Tablets with improved acceptance and good storage stability

ABSTRACT

The present invention relates to tablets for animals, having improved acceptance and good storage stability.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a Continuation application of U.S. patentapplication Ser. No. 14/653,676, filed 18 Jun. 2015, which is a NationalStage entry of International Application No. PCT/EP2013/076878, filed 17Dec. 2013, which claims priority to European Patent Application No.12198101.3, filed 19 Dec. 2012. The disclosure of the priorityapplications are incorporated in their entirety herein by reference.

The present invention relates to tablets for animals, having improvedacceptance and good storage and stability.

Administering tablets to animals is problematic because the animals donot find them attractive at all and generally receive them onlyinvoluntarily. Typically, tablets have to be packed into feed so thatthey can be administered. In this connection, it is not alwaysguaranteed that the drug can be administered in full and thus in theright dose. The release profile of the medicament can also change duringadministration in feed.

EP279343 already discloses active-ingredient combinations composed ofphenylguanidines or benzimidazoles and tetrahydropyrimidines and alsoformulations thereof.

WO 2005/000275 describes tablets containing enrofloxacin and tastesubstances of flavouring substances.

WO 2012/049156 discloses starch-free chewable formulations (“chewables”)containing flavouring substances.

WO 95/20942 describes attractive bait for animals—especially fordogs—into which medicaments can be introduces and thus administered.

Chewable tablets used for administering anxiolytics to domesticatedanimals are described in WO 2010/132286.

As shown, for example, by some of the above-mentioned documents, it isalready known in principle that palatability can be increased byaddition of appropriate flavourings and/or taste substances. However, asa result of said addition, the properties of tablets are frequentlyimpaired to an extent that is not acceptable in practice. For example,tablets having a high proportion of meat flavouring have a tendency toalter their properties during storage. This is due in particular to theageing of the meat flavouring. Owing to the ageing processes of the meatflavouring, the disintegration time of the tablets, for example, can bealtered to an extent that is not acceptable for medicaments. In the caseof tablets which do not contain any meat flavouring, it is generally notdifficult to attain a good storage stability. However, the use of meatflavouring in such tablets entails the difficulties discussed above.

There is therefore a need for highly palatable tablets which satisfy therequirements for medicaments and in particular have a good storagestability.

The invention provides a tablet containing:

-   -   at least one active pharmaceutical ingredient,    -   at least 28% by weight of meat flavouring and    -   at least 2% by weight of a stabilizing agent.

In a further embodiment, the invention provides:

tablets containing:

-   -   at least one active pharmaceutical ingredient,    -   at least 30% by weight of meat flavouring.    -   from 3 to 8% by weight of a stabilizing agent.

According to the invention, the tablets contain at least one activeingredient. The active ingredients can in principle be all possibleactive ingredients which are typically orally administered to animals.

The active ingredients encompass, for example, those against parasites(ectoparasites and/or endoparasites), such as acaricidal, insecticidal,anthelmintic active ingredients; antimicrobial active ingredients, suchas antiviral, antibiotic active ingredients and those effective againstprotozoa, such as Coccidia; in addition, for example anti-inflammatoryand psychotropic active ingredients and also proton pump inhibitors,etc. Examples of suitable active ingredients are the following knownclasses: acaricides, such as the macrocycles abamectin, doramectin,eprinomectin, ivermectin, milbemectin, nikkomycins, selamectin,tetranactin and thmingiensin; bridged diphenyl acaiicides such asazobenzene, benzoximate, benzyl benzoate, bromopropylate, chlorbenside,chlorfenethol, chlorfenson, chlorfensulphide, chlorobenzilate,chloropropylate, dicofol, diphenyl sulphone, dofenapyn, fenson,fentlifanil, fluorbenside, proclonol, tetradifon and tetrasul; carbamateacaricides such as benomyl, carbanolate, carbaryl, carbofuran,fenothiocarb, mcthiocarb, metolcarb, promacyl and propoxur; oximecarbamate acaricides such as aldicarb, butocarboxim, oxamyl,thiocarboxim and thiofanox; dinitrophenol acaricides such as binapacryl,dinex, dinobuton, dinocap, dinocap-4, dinocap-6, dinocton, dinopenton,dinosulfon, dinoterbon and DNOC; formamidine acaricides such as amitraz,chlordimeform, chloromebuform, formetanate and formparanate; grmvthregulators for mites such as clofentezine, dofenapyn, fluazuron,flubenzimine, flucycloxuron, flufenoxuron and hexythiazox;organochlorine acaricides such as bromocyclen, camphechlor, dienochlorand endosulfan; pyrazole acaricides such as acetoprole, fipronil andanalogues and derivatives thereof, tebufenpyrad, pyriprole andvaniliprole; pyrethroid acaricides such as, for example, pyrethroidester acaricides such as acrinathrin, bifenthrin, cyhalothrin,cypermethrin, alpha-cypermethrin, fenpropathlin, fenvalerate,flucythrinate, flumethrin, fluvalinate, tau-fluvalinate and permethrin,pyrethroid ether acaricides such as halfenprox; quinoxaline acaricidessuch as quinomethionate and thioquinox; sulphite ester acaricides suchas propargite; tetronic acid acaricides such as spirodiclofen; andacaricides not belonging to a particular class, such as acequinocyl,amidoflumet, arsenic oxide, chlormethiuron, closantel, crotamiton,diafenthiuron, dichlofluanid, disulfiram, fenazaflor, fenazaquin,fenpyroximate, fluacrypyrim, fluenetil, mesulfen, mnaf, nifluridide,pyridaben, pyrimidifen, sulfiram, sulfluramid, sulphur and triarathene.

Insecticides may belong to various chemical classes, such as, forexample, chlorinated hydrocarbons, organophosphates, carbamates,pyrethroids, formamidines, borates, phenylpyrazoles and macrocycliclactones. Known insecticides include imidacloprid, fenthion, fipronil,allethrin, resmethrin, fenvalerate, permethrin, malathion andderivatives thereof. According to one embodiment, insecticides of theneonicotinoid class are preferred, for example acetamiprid,clothianidin, dinotefuran, imidacloprid (see above), nitenpyram,thiacloprid and thiamethoxam. Frequently used growth-regulating activeingredients (insect growth regulators, IGRs) are, for example,benzoylphenyl ureas, such as diflubenzuron, lufenuron, noviflumuron,hexaflumuron, triflumuron and teflubenzuron or active ingredients suchas fenoxycarb, pyriproxyfen, methoprene, kinoprene, hydroprene,cyromazine, buprofezin, pymetrozine and derivatives thereof.

Anthelmintics may be endoparasiticides or endectocides and encompass thefollowing well-known groups: macrocyclic lactones, benzimidazoles,probenzimidazoles, imidazothiazoles, tetrahydropyrimidines,organophosphates, piperazines, salicylanilides and cyclic depsipeptides(see below).

Preferred anthelmintics encompass macrocyclic lactones having a broadspectrum, such as avermectins, milbemycins and derivatives thereof, suchas, for example, ivermectin, doramectin, moxidectin, selamectin,emamectin, eprinomectin, milbemecin, abamectin, milbemycin oxime,nemadectin and derivatives thereof. The classes of the benzimidazoles,benzimidazole carbamates and probenzimidazoles also encompass activecompounds, such as thiabendazole, mebendazole, fenbendazole,oxfendazole, oxibendazole, albendazole, luxabendazole, netobimin,parbendazole, flubendazole, cyclobendazole, febantel, thiophanate andderivatives thereof. Imidazothiazoles encompass active compounds such astetramisole, levamisole and derivatives thereof. Thetetrahydropyrimidines encompass active compounds such as morantel,pyrantel and derivatives thereof. Organophosphates encompass activecompounds such as dichlorvos, haloxon, trichlorfon and derivativesthereof. Salicylanilides encompass active compounds such as closantel,tribromsalan, dibromsalan, oxyclozanide, clioxanide, rafoxanide,brotianide, bromoxanide and derivatives thereof. Cyclic depsipeptidesencompass compounds having 6 to 30 ring atoms and are composed of aminoacids and hydroxycarboxylic acids as structural units of the ring;examples include PF 1022A, emodepside and others which are described inU.S. Pat. No. 6,159,932, to which reference is hereby expressly made.

Antimicrobial compounds are, for example, various penicillins,tetracyclines, sulphonamides, cephalosporins, cephamycin,aminoglycosides, trimethoprim, dimetridazole, erythromycin, framycetin,furazolidone, various pleuromutilins such as tiamulin, valnemulin,various macrolides, streptomycin, clopidol, salinomycin, monensin,halofuginone, narasin, robenidine, quinolones, etc. Quinolones,preferably fluoroquinolones, encompass compounds which are described inU.S. Pat. Nos. 4,670,444; 4,472,405; 4,730,000; 4,861,779; 4,382,892;and U.S. Pat. No. 4,704,459, to which reference is expressly made.Specific examples of fluoroquinolones include benofloxacin, binfloxacin,cinoxacin, ciprofloxacin, danofloxacin, difloxacin, enoxacin,enrofloxacin, fleroxacin, ibafloxacin, levofloxacin, lomefloxacin,marbofloxacin, moxifloxacin, norfloxacin, ofloxacin, orbifloxacin,perfloxacin, temafloxacin, tosufloxacin, sarafloxacin and sparfloxacin.A further example of an antibacterial fluoroquinolone which can be usedin animals is pradofloxacin. Specific examples of other quinolonesinclude pipemidic acid and nalidixic acid.

Apart from the above-mentioned active pharmaceutical ingredients, it isalso possible to have vitamins or minerals, for example, asconstituents.

The active ingredients may preferably be, for example, depsipeptidesselected from the group consisting of PF 1022A and emodepside.

Preferred antimicrobial fluoroquinolones are in particular enrofloxacinor pradofloxacin.

In a particularly preferred embodiment, the tablets according to theinvention contain an active ingredient selected from febantel, pyrantel(typically in the form of a salt, the embonate being preferred) andpraziquantel or a two-part combination composed of said activeingredients. Even more preferably, febantel, pyrantel embonate andpraziquantel are used as a three-part combination in the tabletsaccording to the invention.

The active ingredients can also—where applicable—be used in the form oftheir salts with pharmaceutically acceptable acids or bases or else assolvates, more particularly hydrates, of the active ingredients or theirsalts.

Prodrugs of the active ingredients can also be used.

According to the invention, the tablets contain at least one activeingredient in a pharmaceutically effective amount, “pharmaceuticallyeffective amount” meaning a non-toxic amount of active ingredient whichcan bring about the desired effect. The amount of active ingredient useddepends on the active ingredient, the animal treated and on the nature,severity and stage of the disease.

In general, the tablets contain about from 0.0001 to 50% by weight ofactive ingredient(s). The tablets can contain from 0.01 to 40% byweight, from 0.1 to 35% by weight, from 1 to 30% by weight, from 5 to30% by weight or from 10 to 30% by weight of active ingredient(s). Infurther embodiments, the tablets can also contain from 1 to 35% byweight, from 5 to 35% by weight or from 10 to 35% by weight of activeingredient(s).

The amount of active ingredient can also be specified as weight pertablet, for example at least 5 mg, at least 10 mg, at least 20 mg, atleast 30 mg, at least 40 mg, at least 50 mg, or at least 100 mg ofactive ingredient(s). For example, the tablets can contain from 5 to2000 mg, from 10 to 1500 mg, from 10 to 1000 mg, from 10 to 500 mg, from20 to 2000 mg, from 20 to 1500 mg, from 20 to 1000 mg, from 20 to 500mg, from 50 to 2000 mg, from 50 to 1500 mg, from 50 to 1000 mg or from50 to 500 mg of active ingredient(s).

Febantel is preferably used in concentrations of from 9 to 20% byweight, preferably from 11 to 17% by weight, particularly preferablyfrom 12 to 16% by weight.

Praziquantel is preferably used in concentrations of from 1 to 10% byweight, preferably from 2 to 8% by weight, particularly preferably from3 to 7% by weight.

Pyrantel, more particularly its embonate, is preferably used inconcentrations of from 8 to 20% by weight, preferably from 9 to 17% byweight, particularly preferably from 11 to 15% by weight.

The tablets according to the invention contain meat flavouring. Meatflavouring refers to an additive which is of synthetic or animal originor a mixture of the two and imparts a meat-like odour and/or taste tothe tablets. Preferably, meat flavourings purely of animal origin areused. These are, for example, prepared from beef, poultry, fish, animalskins or animal livers. Preference is given to so-called desiccatedliver powders, for example from cattle, sheep, poultry or pig andparticularly preferably from poultry or pig.

The meat flavouring is preferably used in an amount of at least 28% byweight, preferably at least 30% by weight, particularly preferably atleast 31% by weight. Typically, not more than 40% by weight of meatflavouring, preferably from 30 to 35% by weight, are used (as elsewhere,percentages here are percent by weight of the finished tablets, unlessotherwise indicated).

Optionally, it is additionally possible to use flavour enhancers suchas, for example, yeast, yeast extracts or glutamate in customaryamounts, for example in concentrations of from 1 to 30% by weight,preferably from 1 to 20% by weight.

Furthermore, the tablets according to the invention contain astabilizing agent. This is to be understood here to mean an excipientwhich improves the shelf life of the tablets. As already explained, thestabilizing agent is required especially in view of the high proportionof meat flavouring. Its aim is especially to prevent or reduce theageing processes which occur in connection with the high proportions ofmeat flavouring. Water-soluble components having a certain action asdisintegrant have been found to be useful. Examples of possiblestabilizing agents are: sugar alcohols, such as xylitol, mannitol orsorbitol; hydrophilic excipients, such as polyethylene glycol,cross-linked polyvinylpyrrolidone; cellulose derivatives such asmethylcellulose, hydroxypropylcellulose (HPC, more particularlylow-substituted, “L-HPC”), hydroxypropylmethylcellulose (HPMC);pregelatinized starch, polyvinylcaprolactam-polyvinylacetate-polyethylene glycol graft copolymer, sodium starch glycolate andcroscarmellose sodium. The preferred stabilizing agent is croscarmellosesodium. The tablets according to the invention contain the stabilizingagent in a proportion of at least 2% by weight, typically from 2 to 15%by weight, preferably from 2 to 10% by weight, particularly preferablyfrom 3 to 9% by weight. In one embodiment, relatively low amounts suchas from 3 to 8% by weight are already sufficient.

The tablets according to the invention can contain further excipients:

Preferably, the tablets according to the invention contain starch or astarch derivative as filler, which also acts to a certain extent as adisintegrant. Starch can, for example, be starch from wheat, rice, corn,tapioca, rye, oats or potatoes. Modified starches can be physicallypretreated starches such as precooked starch or chemically alteredstarches such as hydroxyethyl starch, hydroxypropyl starch, methylstarch, carboxymethyl starch, starch acetate, hydroxypropyl starchacetate, hydroxyethyl starch acetate, starch phosphates, starchsulphates, or chemically or ionically cross-linked starches such asdistarch phosphates, phosphates of hydroxypropylated starches, starchdicarboxylic diesters or salts of anionic starch derivatives.Preferably, starch, such as corn starch for example, is present asfiller, specifically in amounts of typically from 5 to 30% by weight,preferably from 8 to 20% by weight, particularly preferably from 10 to15% by weight, based on the total tablet weight.

The tablets according to the invention further contain a further filler,such as microcrystalline cellulose, maltodextrin; a sugar such assucrose, glucose or lactose; inorganic fillers, such as calciumcarbonate, dicalcium phosphate or magnesium carbonate. Preference isgiven to using microcrystalline cellulose or more particularly lactose.Lactose is a commercially available pharmaceutical excipient which isavailable in various forms, for example spray-dried or as anhydrouslactose. According to the invention, preference is given to usinglactose monohydrate (e.g. milk sugar, fine from DMV International). Thetablets according to the invention contain from 5 to 20% by weight oflactose, preferably from 6 to 15% by weight, particularly preferablyfrom 8 to 12% by weight, based on the total tablet weight.

The tablets according to the invention preferably containmicrocrystalline cellulose or a comparable excipient. Microcrystallinecellulose is a commercially available pharmaceutical excipient (e.g.Avicel® PH 101 from FMC). The tablets according to the invention containfrom 2 to 10% by weight, preferably from 5 to 10% by weight,particularly preferably from 5.5 to 8% by weight, based on the totaltablet weight. In an alternative embodiment, the tablets containpreferably from 3 to 8% by weight and particularly preferably from 4 to6% by weight, based on the total tablet weight.

The tablets according to the invention may preferably contain silicondioxide, more particularly colloidal anhydrous silicon dioxide, inamounts of from 0.01 to 0.3% by weight, more particularly from 0.05 to0.2% by weight, based on the total tablet weight.

The tablets can contain further customary pharmaceutical excipients.Examples of these are: lubricants and glidants such as, for example,magnesium stearate, stearic acid, talc, bentonites; binders such as, forexample, starch, gelatin, cellulose ether or linear polyvinylpyrrolidoneand also dry binders such as microcrystalline cellulose.

Preferably, the tablets according to the invention contain a lubricant,more particularly magnesium stearate, in amounts of from 0.1 to 1.0% byweight, preferably from 0.1 to 0.5% by weight, based on the total tabletweight.

Furthermore, the tablets according to the invention can contain abinder, such as povidone for example. Povidone refers to hydrophilicpolyvinylpyrrolidone polymers, those with a K-value of 30 or lesspreferably being used as binder. Povidone is used in concentrations offrom 0.5 to 5% by weight, preferably from 1 to 3% by weight.

Furthermore, the tablets according to the invention can contain sodiumlauryl sulphate or a comparable excipient. Sodium lauryl sulphate isused in concentrations of from 0.05 to 1% by weight, preferably from 0.1to 0.3% by weight.

If this is required for further therapeutic activities, a further activeingredient can be added to the tablet. If said active ingredient shouldnot be compatible with other ingredients of the tablet, its granules canbe applied or introduced as a separate layer. In this way, a 2-layertablet can be prepared.

Furthermore, the tablet according to the invention can contain at leastone antioxidant in order to avoid the oxidation of the activeingredients. Examples of antioxidants are butylhydroxyltoluene (BHT) andpropyl gallate.

The tablets according to the invention can be prepared according to amethod in which

-   -   (a) the active ingredient(s), and any further excipients, is/are        mixed, granulated, and the granules ground if necessary,    -   (b) the meat flavouring and any further excipients are added to        the mixture from (a) and everything is processed to form a        homogeneous compressible mixture, and    -   (c) the mixture is subsequently processed to form tablets.

In a further embodiment, the tablets according to the invention can beprepared according to a method in which

-   -   (a) the active ingredient(s), and any further excipients, is/are        mixed, granulated, and the granules screened if necessary,    -   (b) the meat flavouring is homogenously mixed and dry granulated        possibly with further excipients,    -   (c) any further excipients are added to the mixture from (a)        and (b) and everything is processed to form a homogeneous        compressible mixture, and    -   (d) the mixture is subsequently processed to form tablets.

Preparation steps (a) can be carried out as wet granulation.Alternatively, preparation steps (a) can be carried out as drygranulation; the missing components are then processed in a separate wetgranulation procedure. It is also possible for all components to be drygranulated with croscarmellose sodium in one step. Thereafter, mixing iscarried out with, for example, magnesium stearate and colloidal silicondioxide to obtain a compressible mixture.

The tablets according to the invention are used for simpleadministration of orally administratable active pharmaceuticalingredients. Therefore, the medicaments according to the invention aresuited to the prophylaxis and treatment of corresponding diseases, andin a preferred embodiment they are used in controlling endoparasites,more particularly helminths, in animals. The compositions according tothe invention are generally suited to use in animal husbandry and animalbreeding in the case of farm animals, breeding animals, zoo animals,laboratory animals, research animals and pets. Preferably, they are usedin animals in which it is to be expected that the meat flavouringadditive improves palatability. These are typically meat caters.

The farm animals and breeding animals include mammals such as, forexample, cattle, horses, sheep, pigs, goats, camels, water buffalos,donkeys, rabbits, fallow deer, reindeer, fur-bearing animals, such as,for example, minks, chinchilla, raccoon.

Laboratory animals and research animals include, for example, mice,rats, guinea pigs, golden hamsters, dogs and cats.

The pets include, for example, dogs and cats.

The compositions according to the invention are particularly preferablyused in dogs and cats, more particularly dogs.

The tablets according to the invention are notable for excellentpalatability. The mechanical properties of the tablets are good. The useaccording to the invention of a stabilizing agent also resulted inmaking the tablets sufficiently storage-stable. Tablets containing nostabilizing agent or an excessively low proportion thereof exhibit achange in disintegration kinetics during storage: the disintegrationtimes of these tablets not in accordance with the invention increasemarkedly, whereas largely constant disintegration times over a storageperiod of at least one year, generally even two years, preferably over 3years, can be achieved with the tablets according to the invention. Thisis achieved by the addition according to the invention of stabilizingagents which can prevent, in the presence of the high proportions ofmeat flavouring, the ageing process which occurs. In case of doubt,disintegration times are determined in accordance with “disintegrationmethod 2.9.1 (Test B)” of European Pharmacopoeia 6, where permissibletolerances for the disintegration times are also specified.

EXAMPLES

(1) (2) (3) (4) (5) (6) Ingredients mg mg mg mg mg mg Febantel 150.0525.0 150.0 525.0 450.0 375.0 Praziquantel 50.0 175.0 50.0 175.0 150.0125.0 Pyrantel 144.0 504.0 144.0 504.0 432.0 360.0 embonate Lactose100.0 350.0 100.0 350.0 300 250.0 monohydrate Corn starch 143.0 500.5143.0 500.5 429.0 357.5 Povidone 25 18.00 63.0 18.00 63.0 54.0 45.0Sodium lauryl 2.0 7.0 2.0 7.0 6.0 5.0 sulphate Spray-dried 355.4 1243.9355.4 1243.9 1066.2 888.5 liver powder Microcrystalline 49.0 171.5 49.0171.5 147.0 122.5 cellulose Croscarmellose 40.0 280.0 50.0 250.0 240.0200.0 sodium Magnesium 3.0 10.5 3.0 10.5 9.0 7.5 stearate Anhydrous 1.03.5 1.0 3.5 3.0 2.5 colloidal silicon dioxide Tablet weight 1055.43833.9 1065.4 3803.9 3286.2 2738.5

Method of Preparation: 1st Preparation Step (“Preblend”)

Praziquantel, febantel and pyrantel embonate and also some of the cornstarch and lactose monohydrate are mixed in a mixer granulator. Themixture is granulated with an aqueous solution of povidone and sodiumlauryl sulphate, subsequently dried and carefully screened.

2nd Preparation Step (“Postblend”)

Meat flavouring, the rest of the corn starch, and the microcrystallinecellulose are dry mixed, compacted and screened.

Preferably, the meat flavouring has in this connection a moisturecontent of at least 5.5% (determined by Karl Fischer titration). Thisgives granules having an acceptable flow behaviour. This is because meatflavouring is hygroscopic and does not flow well as a result. The use ofa wet granulation procedure is less preferred, since the flavouring inthis case loses its volatile components during the drying step.

3rd Preparation Step (“Final Blend” and Compression)

The required amounts of preblend and postblend are mixed withcroscarmellose sodium, magnesium stearate and anhydrous silicon dioxide.This final blend is then processed to form tablets.

Alternatively, preparation step 1 can be carried out as dry granulation.

Instead of preparation step 1 and 2, the components of these two stepscan also be dry granulated with the croscarmellose sodium in one stepand be mixed with magnesium stearate and anhydrous silicon dioxide.

Long-Term Test of Disintegration Properties

FIG. 1 shows the change in disintegration times during a stress test at40° C. of formulations containing different amounts of croscarmellosesodium (AcDiSol). For the data labelled as “40 mg AcDiSol” (40 mg ofcroscarmellose sodium), bone-shaped tablets of the composition accordingto Example 1 were prepared. In the comparative example, the compositionwas maintained apart from the lower amount of 20 mg of croscarmellosesodium (“20 mg AcDiSol”). The tablets were stored at 40° C. over theperiod indicated in days (“Time [d]”); the disintegration propertieswere checked from time to time. The results are shown in FIG. 1.

It is apparent here that the tablets containing 20 mg of croscarmellosesodium (AcDiSol) exhibit, after about 100 days, a distinctly increaseddisintegration time, which increases even more strongly within a periodof over a year. In contrast, the disintegration time of the tabletscontaining 40 mg of croscarmellose sodium (“40 mg AcDiSol”) remainssubstantially constant over the entire period of examination. Since alonger disintegration time in the present case is, inter alia,associated with an altered, in this case delayed, release of the activeingredient and consequently an altogether altered profile of action withrespect to the tablet originally prepared, such an increase or deviationis distinctly disadvantageous. This disadvantage is eliminated by theaccordingly improved storage stability owing to the increased content ofstabilizing agent, in this case with a content of 40 mg ofcroscarmellose sodium for example. With respect to Example 1, the amountof 20 mg of croscarmellose sodium (AcDiSol) corresponds to a content ofless than 2% by weight, based on the total tablet weight.

1. A tablet comprising: at least one active pharmaceutical ingredient,at least 28% by weight of meat flavouring and at least 2% by weight ofstabilizing agent.
 2. The tablet according to claim 1, comprising atleast 30% by weight of meat flavouring.
 3. The tablet according to claim1, comprising from 3 to 8% by weight of a stabilizing agent.
 4. Thetablet according to claim 1, further comprising starch or a starchderivative.
 5. The tablet according to claim 1, further comprisinglactose.
 6. The tablet according to claim 1, comprising at least oneactive ingredient selected from the group comprising: febantel,praziquantel and pyrantel.
 7. The tablet according to claim 6,comprising febantel, praziquantel and pyrantel.
 8. The tablet accordingto claim 6, wherein pyrantel is in the form of pyrantel embonate.
 9. Thetablet according to claim 1 for use in controlling diseases in animals.10. The tablet according to claim 6 for use in controlling helminths inanimals.
 11. A method for preparing the tablet according to claim 1,comprising (a) mixing and granulating the active pharmaceuticalingredient(s) and optionally any further excipients; (b) mixing and drygranulating the animal-derived meat flavouring and optionally, furtherexcipients, with the mixture from (a) to produce a homogenous mixture;(c) adding any further excipients to the mixture produced in (b) to forma homogeneous compressible mixture, and (d) processing the homogeneouscompressible mixture
 12. The tablet according to claim 2, comprisingfrom 3 to 8% by weight of a stabilizing agent.
 13. The tablet accordingto claim 4, further comprising lactose.